The Ganglion Blocking Properties of Homologous Compounds in the Methonium Series

Abstract

Speculation on the relationship of pharmacological activity to chemical structure is a fascinating occupation, though a complex one. An apparently small alteration in molecular configuration may profoundly change the actions of a compound; a well-known example of this is the change in neuromuscular blocking activity brought about by the replacement of methyl by ethyl groups in quaternary ammonium ions (Ing, 1936). In a preceding paper (Wien and Mason, 1951) we found that the ability of hexamethonium to paralyse autonomic ganglia was influenced by the replacement of methyl by ethyl groups on the quaternary nitrogen atoms, and we have now extended our observations to a more systematic study of the tetra-to the heptamethylene members in this alkamethonium series, as well as to several other quaternary ammonium compounds. METHODSThe methods were the same as those described previously (Wien and Mason, 1951) for determining the paralysing effects of substances on transmission through the superior cervical ganglion of the cat; on the peristaltic reflex of the isolated guinea-pig intestine; and on transmission at the neuromuscular junction by the phrenic nerve-diaphragm preparation of the rabbit. Each result in Table I was the mean of several, at least two, experiments on each test object, permitting several comparisons, but no statistical analysis was attempted. In the experiments on the nictitating membrane care was taken to space the injections far enough apart (15 to 20 minutes) to prevent sub-threshold amounts of a previous injection affecting a later one; the order of giving the compound to be tested and the standard for comparison was varied as a further safeguard. Toxicity estimations were determined intravenously in mice.Compounds.-We examined sixteen polymethylene bis-trialkylammonium dibromides of general formula (I), where n=4, 5, 6, or 7, and R=R'=R"=Me, or R=R' =Me and R"=Et, or R=Me and R'=R"=Et, or R =R'=R"=Et. They were all prepared by our colleagues (Barber and Gaimster, 1952).We also examined tetraethylammonium, triethylmethylammonium, diethyldimethylammonium, ethyltrimethylammonium, and tetramethylammonium bromides.The compound y-phenoxypropyltriethylammonium iodide was kindly supplied by Professor

Pharmacological Basis for the Medicinal Use of Ginger in Gastrointestinal Disorders

“…Atropine is also known to block the effect (not the receptors) of nicotine, as the end effect of nicotine in gut preparations is eventually due to release of ACh from myenteric plexus, which in turn activates muscarinic receptors at the end organ (25). To see whether the spasmogenic effect of the plant extract was mediated beyond the level of autonomic ganglia, the tissues were pretreated with hexamethonium (0.3 mM), a ganglion blocker (26). This treatment blocked the effect of nicotine (10 µM), but the effect of the ginger extract remained unaltered (data not shown), suggesting that the plant extract is devoid of any nicotinic effect and the spasmogenic effect observed is mediated through direct stimulation of muscarinic receptors.…”

Pharmacological Basis for the Medicinal Use of Psyllium Husk (Ispaghula) in Constipation and Diarrhea

“…Co-administration of atropine and SB203186 failed to completely block the stimulatory effect of the plant extract and its aqueous fraction, suggestive of some additional mechanism(s) in the spasmodic effect of Ispaghula. To further characterize the stimulatory effect of Po.Cr, the tissue was pretreated with pyrilamine, an H 1 receptor blocker [58], and hexamethonium, a ganglion blocker [59], but the fact that neither of these affected the stimulatory effect of Po.Cr indicates a third component of the stimulatory effect of Ispaghula involving neither histaminic nor nicotinic receptor activation; this remains to be elucidated.…”

Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents

“…However, the efficacy of gut stimulant effect was high in guinea-pig ileum than that found in rabbit jejunum. To further study the nature of the unknown additional spasmodic components, other than cholinergic, the stimulant effect was restudied in the presence of pyrilamine, a histaminic type-1 (H 1 ) receptor blocker [17], hexamethonium, a ganglion blocker [18] or SB203186, a serotonergic (5-HT) receptor antagonist [19]. But VBME showed complete resistance to these antagonists, clearly suggesting some additional mechanism(s), independent of histamine, nicotine or 5-Hydroxytryptamine (5-HT, serotonin) receptors activation.…”